ArticleFluids and barriers of the CNS2022
A transcriptomic analysis of cerebral microvessels reveals the involvement of Notch1 signaling in endothelial mitochondrial-dysfunction-dependent BBB disruption.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 30 citations in OpenAlex.
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- Mitochondrial dysfunction in intracerebral hemorrhage: molecular mechanisms and pathological consequences.Frontiers in cellular neuroscience · 2026Review
- LGALS3 promotes liver fibrosis by enhancing the expression and phosphorylation of ERK1/2.European journal of medical research · 2025Article
- Multi-omics identification and validation of oxidative phosphorylation-related hub genes in schizophrenia.Frontiers in genetics · 2025Article
- Analysis of 90-day risk factors for poor prognosis in patients with postoperative CT with hyperdense signs after thrombectomy for acute ischemic stroke.Frontiers in neurology · 2025Article
- Notch signaling in cancer: metabolic reprogramming and therapeutic implications.Frontiers in immunology · 2025Review
- Barrier genes are associated with preterm birth.Frontiers in medicine · 2025Article
- "Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.Animal models and experimental medicine · 2024Article
- Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.BMC medicine · 2024Article
- Review
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- Prognostic value of nomogram model based on clinical risk factors and CT radiohistological features in hypertensive intracerebral hemorrhage.Frontiers in neurology · 2024Article
- MicroRNA-199a-5p attenuates blood-brain barrier disruption following ischemic stroke by regulating PI3K/Akt signaling pathway.PloS one · 2024Article
- Blood-spinal cord barrier disruption in degenerative cervical myelopathy.Fluids and barriers of the CNS · 2023Review
- Genetic disorders and genetic manipulation at the blood-brain barriers.Fluids and barriers of the CNS · 2023Article
- Research progress on perioperative blood-brain barrier damage and its potential mechanism.Frontiers in cell and developmental biology · 2023Review
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9 authors at 2 institutions in 1 country.
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Abstract
backgroundEndothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood-brain barrier (BBB) disruption. Previous studies have reported that enhancement of mitochondrial function within ECs may reduce BBB disruption and decrease the severity of acute brain injuries. However, the molecular signaling pathways through which enhanced EC mitochondrial function is enhanced to exert this BBB protective effect have not been fully elucidated.
methodsTo identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from TEKCRIF1 KO mice, a mouse strain that displays EC-specific mitochondrial dysfunction. After identification, we assessed the significance of candidate signaling pathways using an intracerebral hemorrhage (ICH) mouse model. BBB integrity was assessed using an IgG leakage assay, and symptomatic changes were evaluated using behavioral assays.
resultsTranscriptome analyses of the TEKCRIF1 KO mouse revealed significant changes in Notch1 signaling, a pathway intimately involved in BBB maintenance. We also observed a decrease in Notch1 signaling and expression of the mitochondrial oxidative phosphorylation (OxPhos) complex in the ICH mouse model, which also exhibits BBB disruption. To further assess the function of Notch1 signaling in relation to BBB disruption, we injected ICH model mice with adropin, a protein that interacts with the Notch1 ligand NB-3 and activates Notch1 signaling. We found that adropin prevented BBB disruption and reduced the extent (area) of the injury compared with that in vehicle controls, in association with alteration of mitochondrial function.
conclusionThese results suggest that the Notch1 signaling pathway acts as an upstream regulator of DEGs and can be a target to regulate the changes involved with endothelial mitochondrial dysfunction-dependent BBB disruption. Thus, treatment methods that activate Notch1 may be beneficial in acute brain injuries by protecting BBB integrity.
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